Low Efficacy of Pegylated Interferon plus Ribavirin plus Nitazoxanide for HCV Genotype 4 and HIV Coinfection

PLoS One. 2015 Dec 7;10(12):e0143492. doi: 10.1371/journal.pone.0143492. eCollection 2015.

Abstract

Background: Nitazoxanide (NTZ) plus pegylated interferon and ribavirin (Peg-IFN/RBV) improved the sustained virological response (SVR) achieved with Peg-IFN/RBV in hepatitis C virus genotype 4 (HCV-4)-monoinfected patients. There are no data currently on the efficacy of Peg-IFN/RBV plus NTZ for human immunodeficiency virus (HIV)/HCV-4 coinfection. Therefore, the objectives of this clinical trial were to assess the efficacy and to evaluate the safety of Peg-IFN/RBV plus NTZ in HIV/HCV-4-coinfected patients.

Patients and methods: This was an open-label, single arm, multicenter phase II pilot clinical trial (NCT01529073) enrolling HIV-infected individuals with HCV-4 chronic infection, naïve to HCV therapy. Patients were treated with NTZ 500 mg bid for 4 weeks, followed by NTZ 500 mg bid plus Peg-IFN alpha-2b 1.5 μg/kg/week plus weight-adjusted RBV during 48 weeks. Analyses were done by intention-to-treat (ITT, missing = failure). A historical cohort of HIV/HCV-4-infected patients treated with Peg-IFN alpha-2b and RBV at the same area was used as control.

Results: Two (9.5%) of 21 patients included in the trial compared with 5 (21.7%) of 23 patients included in the historical cohort achieved SVR (SVR risk difference, -12.2%; 95% confidence interval, -33.2% to 8.8%; p = 0.416). Virological failure was due to lack of response in 13 (62%) individuals recruited in the trial. Two (9.5%) patients included in the trial and two (9.5%) individuals from the historical cohort discontinued permanently due to adverse events.

Conclusions: No increase in SVR was observed among HIV/HCV-4-coinfected patients receiving Peg-IFN/RBV plus NTZ compared with a historical cohort treated with Peg-IFN/RBV. Interruptions due to adverse events of Peg-IFN/RBV plus NTZ were similar to those of dual therapy.

Trial registration: ClinicalTrials.gov NCT01529073.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Coinfection / drug therapy
  • Drug Therapy, Combination
  • Female
  • Genotype
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • Hepacivirus / classification
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / adverse effects
  • Male
  • Middle Aged
  • Nitro Compounds
  • Pilot Projects
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / adverse effects
  • RNA, Viral / blood
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Ribavirin / administration & dosage*
  • Ribavirin / adverse effects
  • Thiazoles / administration & dosage*
  • Thiazoles / adverse effects
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Nitro Compounds
  • RNA, Viral
  • Recombinant Proteins
  • Thiazoles
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2b
  • nitazoxanide

Associated data

  • ClinicalTrials.gov/NCT01529073

Grants and funding

JM is the recipient of a grant from the Servicio Andaluz de Salud de la Junta de Andalucía (B-0037). JAP is the recipient of an intensification grant from the Instituto de Salud Carlos III (grant number Programa-I3SNS). Besides, this work has been partially funded by the RD12/0017/0012 project as part of the Plan Nacional R + D + I and cofinanced by ISCIII- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) (RIS-HEP04). It has been partly supported by grants from Ministerio de Sanidad, Política Social e Igualdad (references EC10-187 and EC11-286). A.R-J is the recipient of a Post-Doctoral Research Extension Grant from the Fundación Progreso y Salud (0028/2013; Consejería de Salud, Innovación y Ciencia de la Junta de Andalucia). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.